Kato et al used LDH and other markers to identify a group of patients with sickle cell disease and chronic intravascular hemolysis. This group is at risk for expressing endothelial dysfunction, which is associated with increased morbidity and mortality. The authors are from the National Institutes of Health, Oakland Children's Hospital and the University of Pittsburgh.


Proposed mechanism: Intravascular hemolysis increases free plasma hemoglobin and arginase, which results in reduced blood nitric oxide (NO). The state of reduced NO bioavailability results in impaired blood flow.


Features of hemolysis-associated endothelial dysfunction:

(1) priapism

(2) leg ulceration

(3) pulmonary hypertension

(4) increased mortality


Markers of intravascular hemolysis:

(1) steady state serum LDH > (mean for the normal range) + (1 standard deviation)

(2) steady state serum AST > serum ALT

(3) anemia with increased reticulocytes

(4) elevated plasma hemoglobin and bilirubin, decreased haptoglobin

(5) low transcutaneous oxygen saturation



• The mean for serum LDH is: ((upper limit for reference range) + (lower limit)) / 2.

• The standard deviation for serum LDH with normal range +/- 2 SD is: ((upper limit for reference range) - (lower limit)) / 4

• The cutoff for LDH above is therefore: ((3 * (upper limit)) + (lower limit)) / 4

• The abnormal laboratory values are steady state values associated with ongoing intravascular hemolysis. This is distinct from the hyperhemolysis that occurs during vaso-occlusive pain crisis (VOC).


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